Breast surgery for metastatic breast cancer

Metastatic breast cancer is not curable, but women with this condition are living longer. While breast surgery is not typically part of the treatment for metastatic disease, retrospective studies suggest it might improve survival. These studies have limitations, including selection bias. A systematic review of randomised controlled trials is needed to assess the benefits and potential harms of breast surgery.

To assess the benefits and harms of breast surgery in women with metastatic breast cancer.

We conducted searches on the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (PubMed), Embase (OvidSP), World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov on 19 April 2023. We conducted searches of conference proceedings, and contacted study authors to identify additional studies.

The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival and toxicity from local therapy.

Two review authors independently assessed studies for inclusion and conducted data extraction, risk of bias assessment, and GRADE assessment of the certainty of the evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes, mean difference (MD) for continuous outcomes and hazard ratio (HR) for time-to-event outcomes. We presented 95% confidence intervals (CI) and used a random-effects model due to expected clinical or methodological heterogeneity among the included studies.

This is the first update of this review and includes three new studies and longer follow-up for two previously included studies. In total, we included five studies with 1368 women: 679 in the breast surgery plus systemic therapy group and 689 in the systemic therapy group. The median follow-up ranged from 3.5 to 10 years. The studies varied in randomisation timing and inclusion criteria. Three studies included women who responded to systemic therapy and excluded those with disease progression, while two included women with untreated metastatic breast cancer. The evidence suggests that breast surgery does not improve overall survival in women with de novo metastatic breast cancer (HR 0.89, 95% CI 0.75 to 1.05; P = 0.09; 5 studies, 1368 women; moderate-certainty evidence, downgraded due to imprecision). Exploratory subgroup analyses suggest potential variation in this finding based on immunohistochemical profile. The addition of breast surgery to systemic therapy may result in a slight improvement in overall survival in women with luminal tumours (HR 0.82, 95% CI 0.69 to 0.96; P = 0.01; 4 studies, 841 women; moderate-certainty evidence), yet this was not observed in women with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative breast cancer. Additional exploratory analyses based on menopausal status and the extent of metastases (i.e. bone-only or multiple sites) suggest that surgery may result in little to no difference in overall survival in these groups. Breast surgery plus systemic therapy may not improve quality of life at six-month follow-up (MD 1.91, 95% CI -2.52 to 6.34; P = 0.40; 2 studies; low-certainty evidence), may give some temporary improvement at 18-month follow-up (MD 6.09, 95% CI 1.90 to 10.28; P = 0.004; 2 studies; low-certainty evidence), which may not be sustained at 24-month follow-up (MD 2.74, 95% CI -2.22 to 7.70; P = 0.28; 2 studies; low-certainty evidence). Breast surgery reduces the risk of local disease progression (HR 0.43, 95% CI 0.32 to 0.58; P < 0.01; 4 studies, 1093 women; high-certainty evidence), but it is unlikely to improve distant progression-free survival (HR 1.19, 95% CI 0.86 to 1.66; P = 0.29; 3 studies; moderate-certainty evidence; downgraded one level due to serious imprecision). An analysis for breast cancer-specific survival was not possible because the included trials did not report data on this outcome. One study assessed toxicity where adding breast surgery to systemic therapy did not seem to have an effect on 30-day mortality (RR 0.99, 95% CI 0.14 to 6.90; 1 study, 274 women; low-certainty evidence, downgraded due to very serious imprecision).

Evidence from five randomised controlled trials suggests that adding breast surgery to the treatment of de novo metastatic breast cancer improves local disease control. Breast surgery does not seem to improve overall survival. However, the effect could vary depending on the immunohistochemical profile; these findings are exploratory and are not definitive. Breast surgery might not affect quality of life, distant progression-free survival or toxicity.